title: Self-assembled dextrin nanogel as protein carrier: controlled release and biological activity of IL-10.
abstract: Interleukin-10 (IL-10) is an anti-inflammatory cytokine, which active form is a non-covalent homodimer. Given the potential of IL-10 for application in various medical conditions, it is essential to develop systems for its effective delivery. In previous work, it has been shown that a dextrin nanogel effectively incorporated and stabilized rIL-10, enabling its release over time. In this work, the delivery system based on dextrin nanogels was further analyzed. The biocompatibility of the nanogel was comprehensively analyzed, through cytotoxicity (lactate dehydrogenase (LDH) release, MTS, Live, and Dead) and genotoxicity (comet) assays. The release profile of rIL-10 and its biological activity were evaluated in vivo, using C57BL/6 mice. Although able to maintain a stable concentration of IL-10 for at least 4 h in mice serum, the amount of protein released was rather low. Despite this, the amount of rIL-10 released from the complex was biologically active inhibiting TNF-α production, in vivo, by LPS-challenged mice. In spite of the significant stabilization achieved using the nanogel, rIL-10 still denatures rather quickly. An additional effort is thus necessary to develop an effective delivery system for this cytokine, able to release active protein over longer periods of time. Nevertheless, the good biocompatibility, the protein stabilization effect and the ability to perform as a carrier with controlled release suggest that self-assembled dextrin nanogels may be useful protein delivery systems.
authors.affiliation: Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
authors.forename: Vera
authors.initials: V
authors.lastname: Carvalho
authors.forename: Pedro
authors.initials: P
authors.lastname: Castanheira
authors.forename: Pedro
authors.initials: P
authors.lastname: Madureira
authors.forename: Sílvia A
authors.initials: SA
authors.lastname: Ferreira
authors.forename: Carla
authors.initials: C
authors.lastname: Costa
authors.forename: João P
authors.initials: JP
authors.lastname: Teixeira
authors.forename: Carlos
authors.initials: C
authors.lastname: Faro
authors.forename: Manuel
authors.initials: M
authors.lastname: Vilanova
authors.forename: Miguel
authors.initials: M
authors.lastname: Gama
mesh_terms: D000818:Animals; D003912:Dextrins / Q000008:administration & dosage* / Q000009:adverse effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000009:adverse effects; D007155:Immunologic Factors / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016753:Interleukin-10 / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000009:adverse effects; D011489:Protein Denaturation; D044967:Serum / Q000737:chemistry
chemical_list: D003912:Dextrins; D004337:Drug Carriers; C556062:IL10 protein, mouse; D007155:Immunologic Factors; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; D016753:Interleukin-10; D011092:Polyethylene Glycols; D011094:Polyethyleneimine